The mechanism by which ovarian hormones affect uterine hemodynamics and myometrial contractility in the rat and dog uterus will be studied by coordinated application of biochemical, physiological and histochemical techniques. The sequence of changes and inter- relationships of catecholamines, progstaglandins and renin-angiotensin will be investigated in the rat during the normal estrus cycle, and as a function of estrogen or combined estrogen-progesterone administration. Catecholamine antagonists, depleting drugs and synthesis inhibitors will be studied for their effects on uterine blood volume and contractility, and prostaglandin levels. Conversely, inhibition of prostaglandin synthesis will be used in a study of effects on catecholamines. The hypothesis that uterine epinephrine exists in a neuronal store and can be synthesized locally will be tested, and the storage sites of uterine epinephrine will be identified histochemically as will sites of synthesis if they are present. The mediation of ovarian hormone effects uterine prostaglandins of the E and F series which will be studied by radioimmunoassay determinations of these compounds during the estrus cycle and upon administration of estrogen or progesterone. In the dog uterus the formation and secretion of renin will be investigated, both in the non-pregnant and pregnant uterus, and the participation of prostaglandins in this phenomenon studied by direct measurement of prostaglandins, and renin by generation of angiotensin I, by radioimmunoassay. The ischemic pregnant uterus will be used as an experimental model for studies of toxemia of pregnancy. Direct measurements of blood flow will be correlated with endocrine state of the animals and formation of prostaglandins and renin.